Philadelphia Positive Acute Lymphoblastic Leukemia, Acute Lymphoblastic Leukemia, Adult
Conditions
Keywords
Ph-Positive Acute Lymphoblastic Leukemia, CAR-T cell, Venetoclax, olverembatinib, Newly Diagnosed
Brief summary
In recent years, immunotherapy (eg. blinatumomab, inotuzumab ozogamicin, CAR-T cells) has demonstrated a high safety and efficacy profile in relapsed/refractory (R/R）B-ALL. The available data suggest that the advancement of immunotherapy from R/R field to the frontline setting may be an important approach to increase the depth of remission, which ultimately translates into a survival benefit. In this study, the investigators propose a treatment regimen using CAR-T cell therapy as a consolidation method for Ph+ ALL patients achieving complete remission (CR) with overembatinib, venetoclax and reduced-intensity chemotherapy, aiming to reduce the total cycles of chemotherapy and related toxicities, shorten length of hospitalization, and ultimately improve patients' survival and quality of life.The study endpoints include 2-year disease-free survival (DFS) rate, overall survival (OS) rate, event-free survival (EFS) rate, cumulative molecular remission rate, immune repertoire-minimal residual disease (MRD) remission rate, cumulative relapse rate, treatment-related toxicities, and quality of life. Additionally, an interim analysis will be conducted, with the 1-year DFS rate as the key index for this analysis.
Detailed description
The CAR-T cells were murine-derived second-generation CD19 CAR-T with a co-stimulation domain of 4-1BB, and the infusion dose was 1×10\^6/kg CAR+ cells in a single infusion.
Interventions
COMBINATION_PRODUCTCAR-T cells
CAR-T cells as consolidation therapy
DRUGVenetoclax
BCL2 inhibitor
DRUGOlverembatinib
TKI
Sponsors
Institute of Hematology & Blood Diseases Hospital, China
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female patients aged 18 years or older 2. Newly diagnosed Philadelphia chromosome positive(either t(9;22) and/or BCR-ABL positive and/ or FISH positive) acute lymphoblastic leukemia 3. CD19 expression on blasts 4. Expected survival time greater than 3 months 5. Adequate end organ function as defined by: Total bilirubin ≤ 1.5 x upper limit of normal（ULN）; serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST) ≤ 2.5 x ULN or ≤5 x ULN if leukemic involvement of the liver is present; Creatinine ≤ 1.5 x ULN; Serum amylase and lipase ≤ 1.5 x ULN; Alkaline phosphatase ≤ 2.5 x ULN unless considered tumor related; normal electrolytes: Potassium ≥ LLN; Magnesium ≥ LLN; Phosphorus ≥ LLN; Cardiac color Doppler ultrasound ejection fraction ≥ 45% 6. Subject has provided written informed consent prior to any screening procedure
Exclusion criteria
1. Lymphoid blast crisis of chronic myelocytic leukemia (CML) 2. Previous or ongoing systemic anti-ALL therapy (including but not restricted to TKI and/or radiotherapy, except for appropriate pre-treatment) 3. Patients with a history of myocardial infarction within 12 months or clinically significant cardiac disorders disease (e.g., unstable angina, congestive heart failure, uncontrollable hypertension, uncontrollable arrhythmia, etc.) 4. Uncontrolled active serious infections that could, in the investigator's opinion, potentially interfere with the completion of treatment 5. Known HIV seropositivity 6. History of acute pancreatitis within 1 year of study screening or history of chronic pancreatitis 7. Uncontrolled hypertriglyceridemia (triglycerides \>450 mg/dL) 8. Another malignancy diagnosed and treated within 5 years prior to diagnosis or previously diagnosed with another malignancy with evidence of residual disease. Patients with non-melanoma skin cancer or any type of carcinoma in situ that has been completely excised should not be excluded 9. Female patients who are pregnant or breast feeding 10. Clinical manifestations of active CNS or extramedullary involvement with ALL 11. Poorly controlled diabetes, defined as glycosylated hemoglobin (HbA1c) values of \>7.5%. Patients with preexisting, well-controlled diabetes are not excluded 12. Any serious psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment 13. Other conditions assessed by the investigators to be inappropriate for this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease-free Survival (DFS) | Up to 2 years post-registration | From CR1 to relapse, death from any cause or last follow-up |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | Up to 5 years post-registration | From the date of registration to the date of death resulting from any cause. |
| Event-free survival (EFS) | Up to 5 years post-registration | From the date of registration to the date of induction failure, relapse, death from any cause, or last follow-up |
| Cumulative rate of complete molecular response | Up to 1 year post-registration | The cumulative rate of patients achieving complete molecular remission |
| MRD-negative complete remission rate measured by NGS tracking clonal IG/TR rearrangements | Up to 1 year post-registration | No clonal IG/TR rearrangements were detected by NGS |
| Cumulative incidence of relapse (CIR) | Up to 2 years post-registration | Calculated with the cumulative incidence method, with death in patients who had a complete hematologic response as a competing risk. |
| The rate of adverse | Up to 5 years post-registration | adverse events during the treatment |
Countries
China
Contacts
CONTACTJianxiang Wang, Dr
PRINCIPAL_INVESTIGATORJianxiang Wang, Dr
Institute of Hematology & Blood Diseases Hospital, China
Outcome results
None listed